The Impact of Blood Pressure on Retinal Vascular Traits: A Mendelian Randomisation Study in Patients with Type 2 Diabetes

Retinal Vascular Traits (RVTs) may provide useful biomarkers of global vascular health allowing patient stratification of cardiovascular disease risk. Blood pressure is a major modifiable determinant of vascular health and various studies have demonstrated significant associations of blood pressure with various RVTs. The extent to which blood pressure causally influences RVTs or the relationship arises through other commonly associated clinical traits is not understood. A Mendelian Randomization study can control for such confounding factors allowing for causality to be determined. In this study, we have created a 262 SNP weighted Genetic Risk Score (wGRS) as instrumental variable for Systolic Blood Pressure (wGRS_SBP) and investigated the impact of this score on RVTs extracted from the retinal photographs of 3950 individuals undergoing diabetes retinal screening from the GoDARTS bioresource. The wGRS was strongly associated with SBP (R2 = 0.0136, p<0.001). In a Mendelian Randomization study using 2 stage least square test (2sls), it was found that AVR and ATORT appear to be directly influenced by SBP. These 2 RVTs may therefore be considered as biomarkers for vascular health influenced by SBP and therefore potentially be used to guide therapeutic decisions to reduce cardiovascular risk by SBP lowering.